Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis

Elizabeth Villa, Jayati Sengupta, Leonardo G. Trabuco, Jamie LeBarron, William T. Baxter, Tanvir R. Shaikh, Robert A. Grassucci, Poul Nissen, Måns Ehrenberg, Klaus Schulten, Joachim Frank

Research output: Contribution to journalArticle

Abstract

In translation, elongation factor Tu (EF-Tu) molecules deliver aminoacyl-tRNAs to the mRNA-programmed ribosome. The GTPase activity of EF-Tu is triggered by ribosome-induced conformational changes of the factor that play a pivotal role in the selection of the cognate aminoacyl-tRNAs. We present a 6.7-Å cryo-electron microscopy map of the aminoacyl-tRNA·EF- Tu·GDP·kirromycin-bound Escherichia coli ribosome, together with an atomic model of the complex obtained through molecular dynamics flexible fitting. The model reveals the conformational changes in the conserved GTPase switch regions of EF-Tu that trigger hydrolysis of GTP, along with key interactions, including those between the sarcin-ricin loop and the P loop of EF-Tu, and between the effector loop of EF-Tu and a conserved region of the 16S rRNA. Our data suggest that GTP hydrolysis on EF-Tu is controlled through a hydrophobic gate mechanism.

Original languageEnglish (US)
Pages (from-to)1063-1068
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number4
DOIs
StatePublished - Jan 27 2009

Keywords

  • cryo-EM
  • Decoding
  • Flexible fitting
  • GTPase
  • Ternary complex

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis'. Together they form a unique fingerprint.

  • Cite this

    Villa, E., Sengupta, J., Trabuco, L. G., LeBarron, J., Baxter, W. T., Shaikh, T. R., Grassucci, R. A., Nissen, P., Ehrenberg, M., Schulten, K., & Frank, J. (2009). Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis. Proceedings of the National Academy of Sciences of the United States of America, 106(4), 1063-1068. https://doi.org/10.1073/pnas.0811370106